論文

査読有り
2017年12月

Histone H3 Threonine 11 Phosphorylation Is Catalyzed Directly by the Meiosis-Specific Kinase Mek1 and Provides a Molecular Readout of Mek1 Activity in Vivo

GENETICS
  • Ryan Kniewel
  • ,
  • Hajime Murakami
  • ,
  • Yan Liu
  • ,
  • Masaru Ito
  • ,
  • Kunihiro Ohta
  • ,
  • Nancy M. Hollingsworth
  • ,
  • Scott Keeney

207
4
開始ページ
1313
終了ページ
1333
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1534/genetics.117.300359
出版者・発行元
GENETICS SOCIETY AMERICA

Saccharomyces cerevisiae Mek1 is a CHK2/Rad53-family kinase that regulates meiotic recombination and progression upon its activation in response to DNA double-strand breaks (DSBs). The full catalog of direct Mek1 phosphorylation targets remains unknown. Here, we show that phosphorylation of histone H3 on threonine 11 (H3 T11ph) is induced by meiotic DSBs in S. cerevisiae and Schizosaccharomyces pombe. Molecular genetic experiments in S. cerevisiae confirmed that Mek1 is required for H3 T11ph and revealed that phosphorylation is rapidly reversed when Mek1 kinase is no longer active. Reconstituting histone phosphorylation in vitro with recombinant proteins demonstrated that Mek1 directly catalyzes H3 T11 phosphorylation. Mutating H3 T11 to nonphosphorylatable residues conferred no detectable defects in otherwise unperturbed meiosis, although the mutations modestly reduced spore viability in certain strains where Rad51 is used for strand exchange in place of Dmc1. H3 T11ph is therefore mostly dispensable for Mek1 function. However, H3 T11ph provides an excellent marker of ongoing Mek1 kinase activity in vivo. Anti-H3 T11ph chromatin immunoprecipitation followed by deep sequencing demonstrated that H3 T11ph was highly enriched at presumed sites of attachment of chromatin to chromosome axes, gave a more modest signal along chromatin loops, and was present at still lower levels immediately adjacent to DSB hotspots. These localization patterns closely tracked the distribution of Red1 and Hop1, axis proteins required for Mek1 activation. These findings provide insight into the spatial disposition of Mek1 kinase activity and the higher order organization of recombining meiotic chromosomes.

Web of Science ® 被引用回数 : 12

リンク情報
DOI
https://doi.org/10.1534/genetics.117.300359
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28986445
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000417013900013&DestApp=WOS_CPL
ID情報
  • DOI : 10.1534/genetics.117.300359
  • ISSN : 0016-6731
  • eISSN : 1943-2631
  • PubMed ID : 28986445
  • Web of Science ID : WOS:000417013900013

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